Half of schizophrenic patients tested in numerous studies have shown absent skin conductance orienting response (SCOR) to neutral tones. Absence of the autonomic OR component related to sympathetic nerve activity maybe a marker for a chronic, non-affective form of illness. Recent advances in diagnosis and in measurement and scoring of autonomic response may contribute to the resolution of current controversies about the OR in psychiatric disorders. The proposed study will evaluate OR abnormalities in 60 Research Diagnostic Criteria (RDC) schizophrenic and 30 major depressed patients, and 30 IQ- and SES-matched normals. Finger pulse volume (FPV) will also be measured; FPV and SC are activated by the same sympathetic nerve bursts, but only one may be present in some subjects under some conditions. SC, FPV and palmar temperature will be recorded during two habituation paradigms of repeated tones (70 dB to elicit the OR, and 103 dB), and during a tone differentiation paradigm. Clinical measures will include SADS, RDC, Family History RDC, and scales that reflect positive and negative symptoms and affective dimensions. Schizophrenics will be classified on Kraepelinian/non-Kraepelinian, acute/chronic, positive/negative and paranoid/non-paraoid dimensions. Drug washout criteria are specified, and serum assay for anticholinergic activity will be carried out to prevent contamination of results by peripheral anticholinergic effects on SC. Major hypotheses include: (1) Schizophrenics will show the highest rate of OR non-response, and group differences will be more robust when occurrence of either FPV or SC response is considered evidence of an OR. (2) Schizophrenics will show the most reduced response to stimuli in the tone differentiation paradigm that have been given significance for the task, supporting Bernstein's (1979) hypothesis that OR hypo-response in schizophrenia is related to deficient mechanisms for the assessment of stimulus significance. (3) Non-habituation of the OR will be absent in schizophrenics when the most valid SC scoring criteria are used. (4) Schizophrenic OR non-responders will have more non-remitting illness and blunted affect and fewer affective features than responders. (5) FPV will be preferentially activated in some subjects with low palmar temperature, primarily non-schizophrenics.